Influence of oxcarbazepine and methsuximide on lamotrigine concentrations in epileptic patients with and without valproic acid comedication: Results of a retrospective study

The aim of this retrospective study was to investigate the influence of oxc arbazepine (OCBZ) and methsuximide (MSM) on lamotrigine (LTG) serum concent rations. The effect of OCBZ compared to carbamazepine (CBZ) and the effect of MSM on LTG serum concentrations were examined in patients with and witho ut valproic acid (VPA) comedication. Altogether, 376 samples from 222 patie nts were analyzed in routine drug monitoring. Two or more serum samples fro m the same patient were considered only if the comedication had been change d. For statistical evaluation, regression analytical methods and an analysi s of variance were performed. For the analysis of variance, the LTG serum c oncentration in relation to LTG dose/ body weight-level-to-dose ratio (LDR) , in (mu g/mL)/(mg/kg)-was calculated and compared for different drug combi nations. The nonlinear regression analysis including the LTG dose per body weight, age, gender, and the different kinds of comedication revealed that these variables have a significant influence on LTG serum concentration (r( 2) = 0.724). The relationship between LTG dose/body weight and serum concen tration deviates only slightly from linearity, the LTG concentration was ab out 18% lower in women than in men, and age had a significant influence. Th e data indicate that children have significantly lower LTG concentrations t han adults on a comparable LTG dose per body weight and that children may b e more prone to enzyme induction by comedicated drugs. Methsuximide has a s trong inducing effect on the LTG metabolism and decreases the LTG concentra tions markedly (about 70% compared to LTG monotherapy). Carbamazepine also reduces the LTG concentrations considerably (by 54%). The inducing effect o f OCBZ (29%) was less pronounced but also significant. The inducing effect of MSM, CBZ, and OCBZ was also seen in combination with VPA: VPA alone incr eases the LTG concentration approximately 211%, whereas in addition to MSM (8%), CBZ (21%), or OCBZ (111%), the increase of LTG was significantly smal ler. The analysis of variance confirmed the results of the regression analy sis. The effect of MSM on the LTG concentration should be considered if MSM is added or withdrawn in patients treated with LTG. Oxcarbazepine had a le ss pronounced inducing effect on LTG metabolism compared to CBZ. if CBZ is replaced by OCBZ as comedication, an increase in LTG serum concentrations s hould be expected.